We request funding to support the 2006 Federation of American Society of Experimental Biologists (FASEB) Summer Conference on "Protein Folding in the Cell" to be held July 29 to August 3, 2006 in Saxtons River, VT. The proposed conference will be the ninth in a series of highly successful FASEB Conferences on this topic. This meeting has been unique in its goal to bring together cell biologists/geneticists, biophysicists/biochemists, and mathematical modelers to tackle the complex problems of protein folding and misfolding and implications for human disease. This was the concept behind the first conference in 1990, and it remains a unique opportunity for scientists from very diverse backgrounds. Most protein folding conferences consider either the theoretical and in vitro aspects of folding or the role of molecular chaperones and protein folding catalysts in the cell. However, the need for interdisciplinary approaches is stronger than ever. The cell biological approaches have progressed to where reaching a mechanistic understanding is crucial, and biological constraints play a critical role in formulating theory and interpreting in vitro data. In addition to examining recent advances in in vitro folding and molecular chaperone mechanism, this meeting will focus on the latest developments in the mechanisms of protein folding and misfolding, and the related cellular processes of protein synthesis, sorting and translocation through the cell and across membranes, macromolecular assembly, and protein degradation. Whereas past "Protein Folding in the Cell" meetings have alternated between emphases on in vitro folding and biophysical topics or cellular aspects of folding in vivo, a new aspect of the 2006 meeting will be to integrate these topics. Common themes include diseases of protein conformation including neurodegenerative diseases, amyloidoses, and cystic fibrosis and how the proteins implicated in these diseases have provided insights into the protein quality control machinery and on the intrinsic properties of folding, misfolding, and assembly into oligomers and fibrils. Finding therapeutic strategies requires a fundamental understanding of the behavior of the polypeptide chain and the cellular environment and constraints imposed on it. Our goal through this meeting is to bring together physical and biological scientists in an interactive environment, to promote education and understanding of the approaches, experimental limitations and to explore common interests. The small size and isolated setting of this meeting with all participants residing and taking their meals in close proximity promotes optimal scientific exchange. The conference format will provide extensive arenas for informal discussions. Poster sessions will allow all participants to interact scientifically with other investigators. Young investigators and women will be well-represented among speakers and encouraged to attend the conference. [unreadable] [unreadable] [unreadable] [unreadable]